+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7mby | ||||||||||||
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タイトル | Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex | ||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN/SIGNALING PROTEIN / GPCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex | ||||||||||||
機能・相同性 | 機能・相同性情報 cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / photoreceptor outer segment membrane / peptide hormone receptor binding / eating behavior / spectrin binding / peptide hormone binding / photoreceptor outer segment / T cell migration / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / cellular response to hormone stimulus / forebrain development / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / cellular response to forskolin / digestion / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / axonogenesis / Regulation of insulin secretion / G protein-coupled receptor binding / peptide binding / neuron migration / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / hormone activity / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / cellular response to hypoxia / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation 類似検索 - 分子機能 | ||||||||||||
生物種 | Rattus norvegicus (ドブネズミ) Homo sapiens (ヒト) | ||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.44 Å | ||||||||||||
データ登録者 | Mobbs, J.I. / Belousoff, M.J. / Danev, R. / Thal, D.M. / Sexton, P.M. | ||||||||||||
資金援助 | オーストラリア, 日本, 3件
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引用 | ジャーナル: PLoS Biol / 年: 2021 タイトル: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. 著者: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / ...著者: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / David M Thal / Laurence J Miller / Patrick M Sexton / 要旨: G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic ...G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from "unwinding" of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs. #1: ジャーナル: Biorxiv / 年: 2021 タイトル: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins: insight into mechanisms of G protein selectivity 著者: Mobbs, J. / Belousoff, M.J. / Harikumar, K.G. / Piper, S.J. / Xu, X. / Furness, S.G.B. / Venugopal, H. / Christopoulos, A. / Danev, R. / Wootten, D. / Thal, D.M. / Miller, L.J. / Sexton, P.M. | ||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7mby.cif.gz | 168.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7mby.ent.gz | 132.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7mby.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7mby_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7mby_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7mby_validation.xml.gz | 38.1 KB | 表示 | |
CIF形式データ | 7mby_validation.cif.gz | 54.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mb/7mby ftp://data.pdbj.org/pub/pdb/validation_reports/mb/7mby | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 BGA
#1: タンパク質 | 分子量: 37416.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnb1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P54311 |
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#2: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
#5: タンパク質 | 分子量: 29144.971 Da / 分子数: 1 Mutation: R39, L41, K343, V346, D347, I358, K380, L384, Q385, N387, E390, N392, V394 represent residues from G(q) 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1, GNAS, GNAS1, GSP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63096, UniProt: P63092 |
-タンパク質・ペプチド / タンパク質 / 非ポリマー , 3種, 3分子 PR
#3: タンパク質・ペプチド | 分子量: 1142.262 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P06307 |
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#4: タンパク質 | 分子量: 47754.867 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CCKAR, CCKRA / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P32238 |
#6: 化合物 | ChemComp-Y01 / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 |
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分子量 | 値: 150 kDa/nm / 実験値: NO | |||||||||||||||||||||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | |||||||||||||||||||||||||||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: TFS KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 63.9 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19_4092: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.44 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 444000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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